| 1. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 2. |
- Asimakopoulou, Eleni Myrto
(författare)
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Search for charged Higgs bosons with tau-lepton signatures at the ATLAS experiment of the Large Hadron Collider and development of novel semiconductor particle detectors
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Experimental High Energy Physics (HEP) studies are discussed in the context of exotic particle searches and data analysis techniques and the development and production of suitable detectors. The main covered topics span the aforementioned areas and are primarily related to the ATLAS experiment at the Large Hadron Collider (LHC).The Higgs boson discovery by the ATLAS and CMS experiments in 2012, solidified the Standard Model (SM), but at the same type provided a suitable probe for searches of new physics, beyond the SM (BSM). This thesis covers a study for a new particle, the charged Higgs boson, which is predicted by several BSM theories and its discovery would be a clear sign for new physics. The study was focused on the predicted τν final state using a 36.1fb−1 dataset of pp collisions collected at √s = 13TeV with the ATLAS detector. No discovery was made, but new limits on relevant parameters were set.Studies that involve hadronically decaying τ leptons, such as the aforementioned charged Higgs boson search, are affected by background processes where quark- and gluon-initiated jets as misidentified as τs. A universal method for determining the impact of this background, and the associated systematic uncertainties, is being developed in ATLAS and is introduced in this thesis.The Large Hadron Collider (LHC) is presently preparing for the High-Luminosity upgrade that is designed to meet the current physics goals. The upgrade will result in more demanding conditions for the LHC experiments, in terms of higher particle fluences and larger collected data volumes, necessitating changes in their detector systems. The ATLAS inner tracker upgrade is discussed, focusing on the workflow and the quality assurance and quality control procedures necessary for the production of the strip modules that will be part of its new end-cap system in collaboration with industry.Neutron detection is essential for a wide range of neutron science applications and research. The evaluation of a novel boron-coated semiconductor with respect to its suitability of neutron detection is discussed.
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| 3. |
- Collins, Elin, et al.
(författare)
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Bridging different realities-a qualitative study on patients' experiences of preoperative care for benign hysterectomy and opportunistic salpingectomy in Sweden
- 2020
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Ingår i: BMC Women's Health. - : BMC. - 1472-6874. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hysterectomy is a common procedure worldwide and removing healthy fallopian tubes at the time of hysterectomy (opportunistic salpingectomy) to possibly prevent ovarian cancer is increasing in frequency, but still controversial. The experiences and perceptions of women, eligible for the procedure, have not been previously investigated. This study aims to, among women waiting to undergo hysterectomy, explore i) experiences and perceptions of self and healthcare in relation to their elective surgery, ii) perceptions of risks and benefits of hysterectomy, including opportunistic salpingectomy.Methods: A qualitative study, with focus group discussions including women < 55 years, planned for hysterectomy with ovarian preservation, was performed. Participants were recruited through purposive sampling from six gynecological departments in different parts of Sweden, including both country and university hospitals. Focus group discussions were conducted using a semi-structured interview guide, digitally recorded, transcribed verbatim and analysed by qualitative manifest and latent content analysis.Results: Twenty-one Swedish-speaking women participated. They were 40-53 years of age, reported varying educational levels, countries of birth and indications for hysterectomy. Analysis rendered a theme "Bridging different realities" over four categories: "Being a woman today", "Experiencing and managing body failure", "Navigating the healthcare system" and "Processing continuously until surgery", including 17 subcategories. The participants displayed varying attitudes towards the significance of their uterus in being a woman. A vague understanding of their body was described, leading to fear related to the reasons for surgery as well as surgery itself. Participants described difficulties understanding and recalling information but also stated that insufficient information was provided. Perceptions of the risks and benefits of opportunistic salpingectomy varied. Involvement in decisions regarding the hysterectomy and potential opportunistic salpingectomy was perceived to be dependent on the counselling gynecologist.Conclusions: The theme Bridging different realities captures the complexity of women deciding on removal of their uterus, and possibly fallopian tubes. It also describes the women's interactions with healthcare and perceived difference between the health professionals and the women's perception of the situation, as viewed by the women. Bridging the different realities faced by patients is required to enable shared decision-making, through sufficient support from healthcare.
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| 4. |
- Collins, Elin, et al.
(författare)
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Menopausal symptoms and surgical complications after opportunistic bilateral salpingectomy, a register-based cohort study
- 2019
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Ingår i: Am J Obstet Gynecol. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 220:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In recent years, the fallopian tubes have been found to play a critical role in the pathogenesis of ovarian cancer. Therefore, bilateral salpingectomy at the time of hysterectomy has been proposed as a preventive procedure, but with scarce scientific evidence to support the efficiency and safety. OBJECTIVE: Our primary objective was to evaluate the risk of surgical complications and menopausal symptoms when performing bilateral salpingectomy in addition to benign hysterectomy. Furthermore, we sought to compare time in surgery, perioperative blood loss/blood transfusion, duration of hospital stay, days to normal activities of daily living, and days out of work for hysterectomy with bilateral salpingectomy compared with hysterectomy only. A secondary objective was to study the uptake of opportunistic salpingectomy in Sweden. STUDY DESIGN: This was a retrospective observational cohort study based on data from the National Quality Register of Gynecological Surgery in Sweden. Women <55 years of age who had a hysterectomy for benign indications with or without bilateral salpingectomy in 1998 through 2016 were included. Possible confounding was adjusted for in multivariable regression models. RESULTS: During the study period, 23,369 women had a hysterectomy for benign indications. The frequency of bilateral salpingectomy at the time of hysterectomy increased mainly from 2013, which is why the period 2013 through mid-2016 was selected for further analysis (n = 6892). There was a low frequency of vaginal hysterectomy with bilateral salpingectomy performed in this period, which is why only abdominal and laparoscopic surgeries were selected for comparative analysis (n = 4906). This study indicates an increased risk of menopausal symptoms (adjusted relative risk, 1.33; 95% confidence interval, 1.04-1.69) 1 year after hysterectomy with bilateral salpingectomy compared with hysterectomy only. Hospital stay was 0.1 days longer in women having salpingectomy (P = .01), and bleeding was slightly reduced in the salpingectomy group (-20 mL, P = .04). Other outcome measures were not significantly associated with salpingectomy, albeit a tendency toward higher risk of minor complications was seen (adjusted relative risk, 1.30; 95% confidence interval, 0.93-1.83). CONCLUSION: Bilateral salpingectomy at the time of hysterectomy was associated with an increased risk of menopausal symptoms 1 year after surgery. Randomized clinical trials reducing the risk of residual and unmeasured confounding and longer follow-up are needed to correctly inform women on the risks and benefits of opportunistic salpingectomy.
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| 5. |
- Collins, Elin, et al.
(författare)
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Physicians' assessment of complications after gynecological surgery in Sweden : The GYNCOM survey
- 2023
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 102:11, s. 1479-1487
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Complications after gynecological surgery in Sweden are registered in the well-established Swedish National Quality Register of Gynecological Surgery, GynOp. The aim of this study was to analyze interrater reliability in assessing complications according to the methods in GynOp, and to explore physicians' perceptions of registering complications.Material and methods: A digital survey was sent to gynecologists and residents in gynecology in Sweden. Participating clinics were recruited through the Swedish network for national clinical studies in Obstetrics and Gynecology, SNAKS. Twenty fictional cases, intended to represent normal postoperative course, failure to cure, and varying degrees of complications, were developed by the research group. The clinical scenarios included abdominal and laparoscopic surgery of the uterus and adnexa, vaginal hysterectomies, as well as hysteroscopy. The respondents graded each case on the presence of a complication (yes/no). Type of complication, severity, and what action the complication required according to Clavien-Dindo was registered if a complication was acknowledged, according to the method in GynOp. Interrater reliability and the opinions of the respondents were presented descriptively. More than 80% of respondents making the same assessment was considered as agreement.Results: The response rate was 41%, with 104 responding physicians from 16 gynecological clinics. Type and severity of complication was considered relevant to register by 88% and 89% of respondents, respectively. Agreement on whether the case described a complication was >80% in 85% (17/20) of cases and agreement using the Clavien-Dindo classification was >90% in 80% (16/20) of cases. There was high agreement in assessments of classically severe complications, such as pulmonary embolism and ureteral damage, in both presence of complication and severity, as well as Clavien-Dindo (>90% for all methods). Cases with agreement <80% on whether the case described a complication were bordering between normal postoperative course and minor complication.Conclusions: This study provides validation for the methods used to register complications after gynecological surgery according to the GynOp register, including the use of Clavien-Dindo in gynecology. However, the results indicate a need to define what should be considered symptoms inherent to each type of surgery.
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| 6. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 7. |
- Idahl, Annika, 1965-, et al.
(författare)
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HOPPSA update: changes in the study protocol of Hysterectomy and OPPortunistic SAlpingectomy, a registry-based randomized controlled trial
- 2023
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The HOPPSA trial is a multi-center national registry-based randomized controlled trial to test the safety and effectiveness of performing opportunistic salpingectomy at hysterectomy to reduce the risk of epithelial ovarian cancer (EOC). The study protocol was first published in January 2019 and is available at . Here, we report amendments made to the study protocol since commencement of the trial.Changes in methods and analysis The primary outcomes analyses have been changed. (1) Complications will be analyzed using binomial generalized estimating equation (GEE) with log link function, while the unadjusted analyses according to Miettinen and Nurminen will be performed as a sensitivity analysis. (2) Absolute change in Menopause Rating Scale (MRS) will primarily be analyzed using a mixed effects model, adjusted for baseline MRS and center as a random effect. (3) Time to EOC will be analyzed using the mixed effects Cox regression model with center as random effect, while the unadjusted log-rank test will be performed as a sensitivity analysis.The primary outcome Complications will be based solely on the specific assessment in the GynOp quality registry. The Clavien-Dindo classification will be evaluated as a secondary outcome.Furthermore, MRS is also measured three years postoperatively to better pinpoint the onset of menopausal symptoms.Discussion The changes to the protocol mainly concern the analyses of data. No changes to recruitment, randomization, intervention, or follow-up of primary outcomes have been made. An interim analysis during 2021 concluded that the study should continue until the target sample size is reached.
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| 8. |
- Iglesias-Gato, Diego, et al.
(författare)
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The Proteome of Primary Prostate Cancer
- 2016
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 69:5, s. 942-952
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clinical management of the prostate needs improved prognostic tests and treatment strategies. Because proteins are the ultimate effectors of most cellular reactions, are targets for drug actions and constitute potential biomarkers; a quantitative systemic overview of the proteome changes occurring during prostate cancer (PCa) initiation and progression can result in clinically relevant discoveries.Objectives: To study cellular processes altered in PCa using system-wide quantitative analysis of changes in protein expression in clinical samples and to identify prognostic biomarkers for disease aggressiveness.Design, setting, and participants: Mass spectrometry was used for genome-scale quantitative proteomic profiling of 28 prostate tumors (Gleason score 6-9) and neighboring nonmalignant tissue in eight cases, obtained from formalin-fixed paraffin-embedded prostatectomy samples. Two independent cohorts of PCa patients (summing 752 cases) managed by expectancy were used for immunohistochemical evaluation of proneuropeptide-Y (pro-NPY) as a prognostic biomarker.Results and limitations: Over 9000 proteins were identified as expressed in the human prostate. Tumor tissue exhibited elevated expression of proteins involved in multiple anabolic processes including fatty acid and protein synthesis, ribosomal biogenesis and protein secretion but no overt evidence of increased proliferation was observed. Tumors also showed increased levels of mitochondrial proteins, which was associated with elevated oxidative phosphorylation capacity measured in situ. Molecular analysis indicated that some of the proteins overexpressed in tumors, such as carnitine palmitoyltransferase 2 (CPT2, fatty acid transporter), coatomer protein complex, subunit alpha (COPA, vesicle secretion), and mitogen-and stress-activated protein kinase 1 and 2 (MSK1/2, protein kinase) regulate the proliferation of PCa cells. Additionally, pro-NPY was found overexpressed in PCa (5-fold, p < 0.05), but largely absent in other solid tumor types. Pro-NPY expression, alone or in combination with the ERG status of the tumor, was associated with an increased risk of PCa specific mortality, especially in patients with Gleason score <= 7 tumors.Conclusions: This study represents the first system-wide quantitative analysis of proteome changes associated to localized prostate cancer and as such constitutes a valuable resource for understanding the complex metabolic changes occurring in this disease. We also demonstrated that pro-NPY, a protein that showed differential expression between high and low risk tumors in our proteomic analysis, is also a PCa specific prognostic biomarker associated with increased risk for disease specific death in patients carrying low risk tumors.Patient summary: The identification of proteins whose expression change in prostate cancer provides novel mechanistic information related to the disease etiology. We hope that future studies will prove the value of this proteome dataset for development of novel therapies and biomarkers. (C) 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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| 9. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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| 10. |
- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 11. |
- Wain, Louise V., et al.
(författare)
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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney
- 2017
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 70:3, s. e4-e19
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.
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| 12. |
- Zeggini, Eleftheria, et al.
(författare)
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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